Unusual Regioselective C-H Difluoroalkylation of Heteroarenes under Photoredox Catalysis.

We disclose a new general strategy for the site-selective difluoroalkylation of nonprefunctionalized heteroarenes, such as quinoxaline at the C-8 position, and benzothiadiazole, benzoxadiazole, and benzothiazole at the C-4 position via consecutive organophotoredox-catalyzed radical-radical cross-coupling and base-assisted hydrogen abstraction reactions. The current methodology represents a site-selective direct difluoroalkylative strategy to allow broad functional group tolerance and a wide substrate scope in good to excellent yields. Careful experimental investigations and detailed DFT calculations revealed the exact site-selectivity of the heteroarenes and a possible mechanistic pathway.

Visible-light-induced Mn(0)-catalyzed direct C-3 mono-, di- and perfluoroalkylation reactions of 2-indazoles.

A general and efficient method for visible-light-driven fluoroalkylation, such as difluoromethylphosphonation, difluoroacetamidation, monofluoromethylation, difluoromethylation, and perfluoroalkyalation, of 2-indazoles using an inexpensive Mn(CO) photocatalyst has been developed. The present methodology affords a new series of C-3 fluoroalkylated 2-indazole derivatives with wide functional group tolerance in good to excellent yields. Difluoromethylenated indiazoles are also prepared from difluoroester derivatives.

Hypervalent iodine(III)-mediated oxidative dearomatization of 2-indazoles towards indazolyl indazolones.

A new iodine(III)-mediated oxidative dearomatization of 2-indazoles has been developed to afford -1 indazolyl indazolones. In this methodology, PIFA plays a dual role: as an oxidant and as a carbonyl oxygen source. A series of indazolone derivatives was promptly synthesized in good to excellent yields through sequential C-heteroatom bond formation.

Remote difunctionalization of 2-indazoles using Koser's reagents.

A new, efficient, and metal-free protocol has been developed for remote difunctionalization of unreactive C-H bonds at the benzene core of 2-indazole by employing Koser's reagents, which act as both sulfonyloxylating and iodinating agents under ambient air. The present methodology represents facile access to C-4-sulfonyloxylated and C-7-iodinated 2-indazole derivatives with high regioselectivity, wide functional group tolerance, and broad substrate scope in good to excellent yields. The formed 4,7 disubstituted 2-indazoles are the precursors of various C-4,7-functionalized 2-indazoles through simple transformations.

Ortho C-H Functionalization of 2-Arylimidazo[1,2-a]pyridines.

C-H activation and functionalization is quite promising in recent days as the strategy offers a go-to general method for different bond formations and hence grants synthetic versatility. At the same time, imidazopyridine, a fused bicycle of imidazole moiety with pyridine ring, has a profound impact due to its ubiquitous and prodigious application in medicinal as well as material chemistry. The presence of N-1 atom in 2-arylImidazo[1,2-a]pyridine facilitates the coordination with metal catalysts leading to the formation of ortho-substituted products.

One-Pot Construction of Indolo[2,3-]quinoxalines through Ruthenium-Catalyzed C-H Bond Functionalization of 2-Arylquinoxalines with Sulfonyl Azides.

The synthesis of N-substituted indolo[2,3-]quinoxalines has been developed through a Ru(II)-catalyzed C-H functionalization of 2-arylquinoxalines with sulfonyl azides and further oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in one pot. This double C-N bond formation strategy provides a new efficient route for the preparation of a series of biologically relevant 6-indolo[2,3-]quinoxaline derivatives in up to 94% yield, suggesting a broad substrate scope applicability. The preliminary mechanistic studies reveal that the sequential C-N bond formations proceed through the formation of a five-membered ruthenacyclic intermediate in the first step and a radical mechanism in the second step.

Potassium Persulfate Mediated Chemodivergent C-3 Functionalization of 2-Indazoles with DMSO as C Source.

A facile, efficient, and transition-metal-free chemodivergent C-3 functionalization of 2-indazoles was developed under aerobic conditions using carboxylic acid and DMSO as the combined source of the carboxylic acid ester group and DMSO as the formylating agent. A series of formylated indazoles and carboxylic acid esters of indazole derivatives were produced in moderate to excellent yields. The mechanistic studies suggest that the reactions probably proceed through a radical pathway.

Ru(II)-Catalyzed Switchable C-H Alkylation and Spirocyclization of 2-Arylquinoxalines with Maleimides via ortho-C-H Activation.

A Ru(II)-catalyzed facile and controllable protocol for C-H alkylation and spirocyclization of 2-arylquinoxalines with maleimides has been achieved under ambient air in high yields. Sequential ortho-C-H activation and -annulation results in the formation of diverse polyheterocycles containing spiro[indeno[1,2-]quinoxaline-11,3'-pyrrolidine]-2',5'-diones, which are of potent interest in medicinal chemistry. Mechanistic investigations suggest a reversible cleavage of the ortho-C-H bond in the turnover-limiting step.

Visible light-induced photocatalytic C-H ethoxycarbonylmethylation of imidazoheterocycles with ethyl diazoacetate.

A visible light-mediated regioselective C3-ethoxycarbonylmethylation of imidazopyridines with ethyl diazoacetate (EDA) was achieved under mild reaction conditions. In contrast to the carbene precursors from α-diazoester a first C3-ethoxycarbonylmethylation of imidazopyridines a radical intermediate has been established. The present methodology provides a concise route to access pharmacologically useful esters with wide functional group tolerance in high yields.

Organophotoredox-Catalyzed C(sp)-H Difluoromethylenephosphonation of Imidazoheterocycles.

A mild and efficient method for the direct difluoromethylenephosphonation of imidazopyridines has been developed using rose bengal (RB) as a photoredox catalyst. Bis(pinacolato)diboron (Bpin) is found to be a crucial additive in the present reaction. The present methodology is also applicable to other heterocycles like imidazo[2,1-]thiazole, benzo[]imidazo-[2,1-]thiazole, and indole.

Visible-Light-Induced Regioselective Cross-Dehydrogenative Coupling of 2 H-Indazoles with Ethers.

A visible-light-promoted regioselective C(sp)-H/C(sp)-H cross-dehydrogenative coupling between 2 H-indazoles and ethers has been achieved using a catalytic amount of rose bengal as an organophotoredox-catalyst and tert-butyl hydroperoxide (TBHP) as an oxidant at ambient temperature under aerobic conditions. A variety of C-3 oxyalkylated 2 H-indazoles have been synthesized in moderate to good yields. Mechanistic studies suggest a radical pathway of the present reaction.